Targeting Neutrophil Extracellular Traps to Mitigate Post-Traumatic Lower-Extremity Soft Tissue Injury
Abstract
Tissue damage from musculoskeletal trauma often includes a secondary ischemia-reperfusion (IR) injury, which results in fibrosis and loss of function in the skeletal muscle. Here, we investigate strategies to mitigate skeletal muscle fibrosis caused by IR injury by targeting neutrophil extracellular trap (NETs) formation via PAD4 and TLR9 mechanisms. We show that muscle fibrosis is largely independent of PAD4 and TLR9 mediated NET formation. Importantly, we identify administration of FDA-approved Plaquenil(hydroxychloroquine) as a promising treatment strategy to reduce fibrosis. In mouse models, treatment with Plaquenil decreased skeletal muscle fibrosis and improved myofiber regeneration following IR injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2021
- Accession Number
- AD1118647
Entities
People
- Benjamin Lévi
Organizations
- University of Michigan